Aminoacetobiphenyl compounds



Patented Feb. 27, 1951 UNITED STATES "?PATE N T 'OLFFZICEAMINQACETOBIPHENYL COMPOUNDS LouisL. Bamba-s, Grosse Pointe Woods, Mich,as-

;signor to Parke, .Davis & Company, Detroit,

Mich., acorporation of Michigan No Drawing. Application vJanuary' i,1950, Serial No. 136,831

11 Claims.

This application is a-'continuation-in-.-part of my copendingapplication Serial No. 83,778, filed March 26, 1949, now U. S. Patent2,516,098, and

the invention relates to acid addition salts of certain ketonic aminesand to methods for. obtaining the same.

lates to acid addition salts of biphenyl aminomethyl ketones having theformula,

wherein R and n have the same significance as given above and X is ahalogen atom. This vhydrolysis may be carried out in aqueous ononaqueous reaction mixtures using 'an inorganic mineral acid as thehydrolytic agent. Any mineral acid can be used,.for example,hydrochloric, hydrobromic, hydroiodic, sulfuric or phosphoric acids canbe employed. Regardless of the acid selected as the hydrolysis catalyst,therbiphenylyl aminomethyl ketone acid addition "salt formed consistsprincipally of the salt-corresponding to the acid used in thehydrolysis. .For the best yields of the desired products it ispreferable to use an alcoholic reaction-medium. The function of thealcohol present in such reaction media is to remove-the formaldehydeformed in .the reaction as the acetal and thus prevent'its reaction witheither the startingmaterial .orjl'inalproduct. Reaction mixturesconsisting'of or 'containing'alcohols such as methanol, ethanol,n-propanol, isopropanol, n-butanol and the like produce particularlygoodresults.

The hydrolysis'reaction can be carried out at temperatures varying fromabout toi11 0 C. However, I prefer to use a temperature of about 20 to80 C. since in this temperature range the reaction proceeds at areasonable rate and the danger of decomposition of .the startingmaterial and/or the final product'is almost at a minimum.

The products of the invention'are useful'as intermediates in thepreparation of other organic compounds. They are of particular'value inthe More particularly, the invention re 1 antibiotic "activity againstmicroorganisms .Ofthe 'Rickettsia type.

The invention is illustrated by the "following examples.

.E:cample 1 175 g. of the 4-biphenylyl bromomethylketonehexamethylenetetramine complex is added to 200 cc. ofconcentratedhydrochloric acid in 1 liter of absolute alcohol and themixturestirred over- ;night. The insoluble. hydrochloride salt of4-biphenylyl aminomethyl ke-tone is 'collected 'by fil- -tration, washedwith a small amount of cold water and dried at room temperature.

Thejformula of this product is,

Example-.2

175 g. of '3-biphenylyl bromomethyl -ketonehexamethylenetetraminecomplex is mixed with a cold solution of 1 liter of absolute alcoholand.

200 cc. of concentrated hydrochloric acid and the mixture stirredovernight at room temperature. The :solid product which-consists of thhydrochloride. salt of '3-biphenylyl aminomethyl ketone is collected,washed with 200 cc. of ice cold water :to remove the ammonium .chlorideand dried. The formula ofthis compound is,

Example 3 100 g. of 4'-methoxy-4-biphenylyl bromomethylketone-hexamethylenetetramine complex is mixed with a cold solution of500 cc. of absolute ethanol and 100 cc. of concentrated hydrochloricacid and themixture stirred overnight at room temperature. The solidproduct which consists of the hydrochloride salt of 4 -methoxy-4-biphenylyl aminomethyl ketone contaminated with ammonium chloride iscollected, washed -with cold water to remove the ammonium chloride-anddried. The formula of this product is,

Example 4 Y acid andthe mixture stirred .overnight-at-room preparationof organic compounds possessing temperature. .The solid product whichconsists of the'hydrochloride salt of 4'-nitr.o-4-biphenyly1.aminomethyl ketone contaminated with ammo- 3 nium chloride iscollected, washed with ice water to remove the ammonium chloride anddried. The formula of this hydrochloride salt is,

Example 5 135 g. of 4-iodo-4-biphenylyl bromomethyl ketonehexamethylenetetramine complex is mixed with a cold solution of 1 literof absolute alcohol and 200 cc. of concentrated hydrochloric acid andthe mixture stirred overnight at room temperature. The solidhydrochloride salt of 4'-iodo-4-biphenylyl aminomethyl ketone whichseparates is collected, washed with cold water to remove the ammoniumchloride and dried. The formula of this product is,

O t I C H NHz'H Cl Example 6 175 g. of 2'-methyl-4-biphenylylbromomethyl' ketone hexamethylenetetramine complex is added to 1 literof methanol and 200 cc. of 12 N sulfuric acid and the resulting mixturestirred overnight at room temperature. The insoluble2'-methyl-4-biphenylyl aminomethyl ketone sulfate is collected, washedwith a small amount of water and dried in vacuo. The formula of thisproduct is,

ll OQo-omrrm-wmsm Example 7 A mixture consisting of 200 g. of4'-nitro-6- methyl-3-biphenylyl bromomethylketone-hexamethylenetetramine complex, 200 cc. of concentratedhydrochloric acid and 1 liter of isopropanol is stirred overnight atroom temperature. The insoluble product is collected, washed with coldwater to remove the ammonium chloride and dried. This product is thehydrochloride salt of 4'-nitro-6-methyl-3-biphenylyl aminomethyl ketoneof formula,

Example 8 85 g. of Z-biphenylyl bromomethyl ketonehexamethylenetetraminecomplex is added to 100 I cc. of constant boiling hydrobromic acid in750 cc. of absolute alcohol and the mixture stirred overnight. Theinsoluble hydrobromide salt of Z-biphenylyl aminomethyl ketone iscollected by filtration, washed with a small amount of cold water anddried at room temperature. The formula of this product is,

The biphenyl halomethyl ketone-hexamethylenetetramine complexes used asstarting materials in the practice of the invention may be prepared byreacting a biphenylyl halomethyl ketone I OQd-omwnmm-m What I claimis: 1. A mineral acid addition salt of a compound of the formula,

where n is one of the integers 1 and 2 and R is a member of the classconsisting of hydrogen, halogen, NO2, lower allzyl and lower alkoxyradicals.

2. A mineral acid addition salt of a compound of the formula,

3. l-biphenylyl aminomethyl ketone hydrochloride.

4. A mineral acid addition salt of a compound of the formula,

5. 3 -biphenylyl aminomethyl ketone hydrochloride.

6. A mineral acid addition salt of a compound of the formula,

7. 4'-nitro-4-biphenylyl aminomethyl ketone hydrochloride.

8. A mineral acid addition salt of a compound of the formula,

9. 4-iodo-4-biphenylyl aminomethyl ketone hydrochloride.

10. A mineral acid addition salt of a compound of the formula,

11. 4-meth0xy-l-biphenylyl aminomethyl ketone hydrochloride;

LOUIS L. BAMBAS.

REFERENCES CITED The following references are of record in the file ofthis patent:

Chemical Abstracts, vol. '7 (1913), p. 1713.

Chemical Abstracts, vol. 32 (1938), page 5825.

1. A MINERAL ACID ADDITION SALT OF A COMPOUND OF THE FORMULA,